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Biomedical subjects

C D Lothrop

Publications and source records attributed to C D Lothrop.

At least 55 records · Page 3Linked to original sources

Equine thyroid function assessment with the thyrotropin-releasing hormone response test.

The effect of thyrotropin-releasing hormone (TRH) on equine thyroid function was determined by quantifying serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) before and after TRH administration. Thyrotropin-releasing hormone was administered IV to adult horses (n = 5) and ponies (n = 6) at a dose of 1 mg or 0.5 mg, respectively. Serum T4 and T3 concentrations were determined before and 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after TRH administration. Serum T4 increased from a basal concentration of 24.4 +/- 8.7 ng/ml (mean +/- SD) to a maximum value of 48.2 +/- 10.2 by 4 hours after TRH administration. Serum T3 increased from a basal concentration of 0.44 +/- 0.18 ng/ml to a maximum value of 1.31 +/- 0.37 ng/ml by 2 hours after TRH administration. Seemingly, TRH increases serum concentrations of T4 and T3 and may be useful as a test of equine hypophysis-thyroid function.

Aging↗

Evaluation of adrenal function in psittacine birds, using the ACTH stimulation test.

The effect of ACTH (16 units) on plasma cortisol and corticosterone concentrations in healthy psittacine birds was evaluated. Plasma corticosterone significantly increased (P less than 0.01) from a mean (+/- SD) basal concentration of 3.25 +/ 3.6 ng/ml to 26.47 +/- 9.25 (one hour after ACTH administration) and 25.69 +/- 13.23 ng/ml (2 hours after ACTH administration). For maximal increase in plasma corticosterone as measured by radioimmunoassay (RIA), heat denaturation was necessary to release corticosteroids from steroid-binding proteins. As measured by RIA, plasma cortisol concentrations did not increase, whether or not the heat denaturation step was included. Addition of cortisol to avian plasma did not prevent accurate quantification of cortisol as measured by RIA. Plasma corticosterone concentrations in cockatoos, macaws, Amazon parrots, conures, and lorikeets before and after ACTH administration indicated that the ACTH stimulation test could be used to evaluate adrenal secretory capacity in psittacine birds.

Adrenal Cortex Function Tests↗

Thyrotropin stimulation test for evaluation of thyroid function in psittacine birds.

Serum thyroid hormone concentrations were determined before and after thyrotropin (thyroid stimulating hormone [TSH]) stimulation in caged psittacine birds to determine whether the TSH stimulation test could be used to evaluate thyroid function in this class of birds. The mean (+/- SD) resting thyroxine concentrations (ng/ml) for the species studied were: cockatoos, 13.63 +/- 6.53 (n = 6); Amazon parrots, 8.19 +/- 6.90 (n = 8); scarlet macaws, 1.34 +/- 0.51 (n = 9); blue and gold macaws, 3.41 +/- 1.78 (n = 8); African gray parrots, 1.42 +/- 0.44 (n = 6); conures, 1.76 +/- 0.77 (n = 5); and cockatiels, 11.83 +/- 6.76 (n = 3). The mean (+/- SD) thyroxine concentrations (ng/ml) 4 to 6 hours after TSH stimulation were 35.10 +/- 13.16, 27.40 +/- 15.93, 6.46 +/- 3.10, 12.36 +/- 6.34, 9.30 +/- 2.90, 13.50 +/- 7.71, and 39.0 +/- 5.66, respectively. Serum tri-iodothyronine concentration did not increase significantly after TSH stimulation. The results demonstrated that the TSH stimulation test can be used to evaluate thyroid function in caged psittacine birds.

Animals↗

Diagnosis of canine Cushing's syndrome based on multiple steroid analysis and dexamethasone turnover kinetics.

A comparison of cortisol concentrations, determined by high-performance liquid chromatography (HPLC) and radioimmunoassay, was made in healthy, mixed-breed dogs and in dogs with clinical signs of Cushing's syndrome. Absolute concentration of cortisol was less in resting, dexamethasone-suppressed, and ACTH-stimulated plasma samples, when measured by HPLC relative to cortisol concentrations determined by radioimmunoassay. Diagnosis of Cushing's syndrome could be made using either method. Plasma concentrations of cortisone and corticosterone were determined by HPLC. Cortisone and corticosterone concentrations alone were not diagnostic of Cushing's syndrome; but when used in conjunction with cortisol determinations, they provided additional criteria for laboratory confirmation of the clinical diagnosis of Cushing's syndrome. The clearance of exogenous dexamethasone used in the dexamethasone-suppression test was examined in the normal and cushingoid dogs. Plasma concentrations of exogenous dexamethasone were constant during the 3-hour test in the normal dogs. However, in 75% of the dogs with Cushing's syndrome, exogenous dexamethasone was cleared completely in the 3-hour test. Thus, dexamethasone clearance rates were excessively fast in most dogs with Cushing's syndrome.

Adrenal Cortex Function Tests↗

Canine and feline thyroid function assessment with the thyrotropin-releasing hormone response test.

A canine and feline pituitary-thyroid function test based on thyrotropin-releasing hormone (TRH) stimulation of endogenous thyrotropin is described. Serum thyroxine is measured before and after stimulation with TRH. A positive response to TRH indicated a functionally intact pituitary-thyroid axis. At TRH doses of 0.002 to 10.0 mg/kg of body weight, dose response of serum thyroxine to TRH stimulation was determined. Increasing the dose of TRH increased the duration, but not the magnitude, of thyroxine stimulation. At TRH doses greater than 0.1 mg/kg, drug side effects were salivation, defecation, urination, vomition, miosis, tachycardia, and tachypnea. A useful procedure for pituitary-thyroid function testing was serum thyroxine measurement before and 6 hours after TRH (0.1 mg/kg) stimulation.

Animals↗

RNA turnover in cultured hamster embryo cells: identification of modified nucleoside end products.

Fourteen methylated nucleosides (N-2-dimethylGuo, N-2-methylGuo, N-1-methylGuo, N-5-methylUrd, N-3-methylUrd, N-1-methylAdo, N-3-methylCyd, N-5-methylCyd, N-1-methyllno, 2'-Omethyl-Cyd, 2'-O-methylUrd, 2'-0-methylGuo, 2'-0-methyllno, and thymidine) and one methylated base (m7Gua) have been identified as normal excretion products of cultured hamster embryo cells. The methylated nucleosides are excreted in the culture media subsequent to RNA turnover. The excretion pattern of the base-methylated nucleosides was determined by continuous labeling of serum-stimulated quiescent hamster embryo cells with [3H-CH3]methionine and measurement of radioactivity in the excreted nucleosides between 23 and 81 1/2 hours after the label was added. These nucleosides accumulate exponentially until a maximum level is reached after 60 hours. These maximum levels were maintained for at least an additional 20 hours.

Animals↗

Salvage of the modified nucleoside ribothymidine in cultured hamster embryo cells.

RNA turnover in hamster embryo cells results in the release of ribothymidine, a methylated nucleoside formed only on intact RNA. [methyl-3H]Methionine ribothymidine polyphosphates and deoxyribothymidine polyphosphates are found in approximately equivalent amounts in the acid-soluble pool of hamster embryo cells. This observation is consistent with prior unexplained observations, in intact animals, that the methyl group of S-adenosyl methionine can be used for deoxythymidine synthesis, This is the only modified ribonucleoside known to be salvaged through pathways in normal cells. Several possible pathways for salvage were investigated.

Animals↗

Rapid preparation of nucleotides from acid-soluble pools by chromatography on silica, as exemplified with acid extracts of cultured cells.

A rapid technique (5-10 min) has been developed for fractionating nucleotides from base and nucleoside contaminants in acid extracts of cells, by adsorption to silica gels. Silica gels (1-mL bed volume) were washed with 5 mL of water then with 5 mL of acetonitrile/water (90/10 by vol). After applying 3-mL samples, adjusted to 900 mL/L acetonitrile content, we washed the gel with an additional 10 mL of the acetonitrile/water solvent. More than 95% of the amounts of bases and nucleosides prsent, except for cytidine (92%), did not adsorb to silica under these conditions. Nucleotides were then quantitatively eluted with 9 mL of water. The retention volumes for positive, negative, and neutral nucleic acid components have been determined, to investigate the discriminatory properties of nucleic acid components on silica. Compounds (bases, nucleosides) that are not ionized at pH 7 do not bind to silica. However, negative, positive, and zwitterionic compounds are tightly adsorbed to the silica gels. This procedure has been used to purify nucleotides from several normal and transformed cell lines.

Animals↗

The use of radionuclide angiography to study blood flow through endothelial cell seeded extrathoracic bypass grafts in the dog.

Endothelial seeding of vascular grafts has been shown to decrease graft thrombogenicity and prolong longevity when implanted in vivo. Previous studies have utilized anatomic grafts to study endothelialization and healing. Anatomic thoracoabdominal grafts do not allow for sequential biopsy for evaluation of individual grafts nor do they approximate the environment for long bypass grafts used in limb salvage. This study evaluated the use of an extra-anatomic aortic bypass graft to assess the healing of endothelial cell seeded expanded polytetrafluoroethylene (ePTFE). Radionuclide angiography was used to evaluate graft patency and quantify blood flow through the graft. Dogs underwent placement of an extra-anatomic 60 cm long, 8 mm internal diameter, graft seeded with autologous endothelium. Grafts were biopsied from 2 weeks up to 1 year. Radionuclide studies were performed postimplantation and following each graft biopsy. Graft placement and biopsies were well tolerated in all dogs. Biopsied segments of graft allowed for sequential studies of the healing of implanted grafts by scanning electron and light microscopy. Flow through the implanted graft was close to 50% of the total caudal abdominal aortic flow. No significant difference in graft flow was noted either between animals or over time.

Anastomosis, Surgical↗

A retrospective study of aldosterone secretion in normal and adrenopathic dogs.

A retrospective study on stored plasma from normal dogs and dogs with pituitary dependent hyperadrenocorticism (PDH), pituitary dependent hyperadrenocorticism controlled by mitotane (o,p'-DDD),* iatrogenic hyperadrenocorticism, and hypoadrenocorticism was conducted to determine if alterations in aldosterone production exist in these disorders. The plasma aldosterone concentration (PAC) was measured by radioimmunoassay immediately before and 1 hour after adrenocorticotropic hormone (ACTH) administration (0.5 IU/kg, intravenously [IV]). PACs increased significantly when ACTH was administered to normal dogs. Dogs with PDH had a lower baseline PAC, but their PAC increased to levels similar to that of normal dogs after ACTH administration. In dogs with PDH controlled by o,p'-DDD therapy, the response to ACTH was significantly less than that of normal dogs or dogs with untreated PDH. Dogs with iatrogenic hyperadrenocorticism had a lower baseline and post-ACTH PAC than normal dogs. Dogs with hypoadrenocorticism had a normal basal PAC, but showed no significant increase in PAC following ACTH administration. These findings suggest that PACs are significantly altered in a variety of adrenal diseases, and that the ACTH stimulation test may be useful when evaluating aldosterone secretion in adrenopathic disorders. In addition, at therapeutic dosages, o,p'-DDD treatment was associated with a decrease in basal and post-ACTH PACs in dogs with PDH.

Adrenal Cortex↗

Acromegaly in 14 cats.

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).

Acromegaly↗

Increased serum growth hormone concentration in feline hypertrophic cardiomyopathy.

Serum growth hormone concentration was measured by radioimmunoassay in 31 cats with hypertrophic cardiomyopathy, 38 normal cats, and 35 cats with other cardiac disease. Cats with hypertrophic cardiomyopathy had a significantly increased serum growth hormone concentration when compared with normal cats and cats with other cardiac disease. The serum growth hormone concentration in cats with hypertrophic cardiomyopathy was less than that previously reported in cats with growth hormone secreting pituitary tumors. Pituitary tumors were not identified in eight of the cats with hypertrophic cardiomyopathy examined at necropsy. An increased serum growth hormone concentration may be measured in cats with hypertrophic cardiomyopathy but it is unclear if the increased serum growth hormone concentration is a cause or effect of hypertrophic cardiomyopathy.

Acromegaly↗

Serum erythropoietin concentrations measured by radioimmunoassay in normal, polycythemic, and anemic dogs and cats.

Serum erythropoietin (Epo) concentrations were measured by radioimmunoassay (RIA) in normal, polycythemic, and anemic dogs and cats. The serum Epo concentration in normal dogs (n = 25) ranged from 7 to 37 mU/mL (median, 20 mU/mL); and in normal cats (n = 11) ranged from 9 to 38 mU/mL (median, 18 mU/mL). Polycythemic animals (PCV > 55% in dogs, > 45% in cats) were classified as those with primary (polycythemia vera), secondary, or polycythemia of uncertain etiology. Dogs with polycythemia vera (PV, n = 8) had a median serum Epo concentration in the normal range (17 mU/mL); cats with PV (n = 7) also had a median serum Epo concentration that was within the normal range (10 mU/mL). In the category of secondary polycythemias, dogs (n = 7) (median, 30.7 mU/mL) and cats (n = 2) had normal Epo concentrations. The median serum Epo concentration was significantly decreased (P < .05) in dogs with PV compared with dogs with secondary polycythemias. The median serum Epo concentrations in dogs (n = 13) and cats (n = 5) with anemias not due to chronic renal disease were significantly increased (P < .05) compared with normal dogs and cats. In cats with anemias due to chronic renal disease (n = 5) the median serum Epo concentration was not significantly different from normal cats. The measurement of the serum EPO concentration may be useful in assessment of anemia or polycythemia but the overlap of values with the normal range in all groups evaluated limit its diagnostic use.

Anemia↗

Synthetic vascular grafts seeded with genetically modified endothelium in the dog: evaluation of the effect of seeding technique and retroviral vector on cell persistence in vivo.

Unique characteristics of endothelium make it an attractive target cell for gene transfer. Genetically modified endothelial cells (ECs) seeded on synthetic vascular grafts offer the potential to control neointimal hyperplasia, decrease graft thrombogenicity and improve small diameter graft patency. This study addresses the issue of synthetic vascular graft colonization with endothelial cells transduced with noninducible retroviral marker genes in the dog. Autologous endothelial cells were enzymatically harvested and transduced with either the bacterial NeoR gene or human growth hormone gene using retroviral vectors. All transduced cells were positive by polymerase chain reaction (PCR) amplification for the transduced gene sequence prior to graft seeding. Transduced ECs were seeded on Dacron grafts (n = 3) preclotted with autologous blood. These grafts exhibited complete endothelialization at times from 250 to 360 days. Recovered DNA, however, was negative for the transduced gene sequence when analyzed by PCR and Southern blotting. Expanded polytetrafluoroethylene (ePTFE) was evaluated (n = 8) using several different cell seeding protocols. Grafts were seeded at 3 densities (ranging from 6 x 10(3) to 1.5 x 10(5) cells/cm2) and 2 different adherence times. Seeding substrate was also evaluated. Grafts were either preclotted with whole blood or incubated with 20 or 120 micrograms/ml fibronectin for 60 min. Graft biopsies were evaluated from 2 to 52 wk. Limited endothelialization was present in 4 dogs as early as 2 wk, but never progressed to full luminal coverage. The remaining dogs failed to ever exhibit any luminal EC adherence. Two dogs with limited EC coverage had positive DNA by PCR for the NeoR gene sequence at 2 and 3 wk. In contrast to transduced EC's, nontransduced EC colonization of ePTFE was complete at 2 wk when seeded under conditions that transduced cells had failed to persist. Neither seeding density, adherence time, seeding substrate or retroviral vector used influenced the uniformly poor graft coverage seen with transduced cells. Results of this study indicate that despite successful gene transfer using 4 different retroviral vectors, transduced endothelial cells seeded under varying conditions appear altered in their ability to stably adhere and colonize synthetic vascular grafts in vivo.

Animals↗

Determination of normal values using an automated coagulation timer for activated coagulation time and its application in dogs with hemophilia.

The present study was performed to determine normal values for the Medtronic HemoTec automated activated coagulation time (ACT) analyzer (Medtronic HemoTec Inc, Parker, CO, distributed in Switzerland by Convergenza AG, Vaduz, Liechtenstein), and to evaluate its ability to detect dogs with hemophilia. ACT was measured in 43 healthy dogs presented to the Companion Animal Hospital, University of Bern, Bern, Switzerland, with the Medtronic HemoTec ACT analyzer to determine normal values. The mean +/- 2 standard deviations (SDs) of the values obtained was defined as the normal range. ACT was measured 8-10 times on the same day in 6 dogs to determine repeatability. ACT also was measured in 11 dogs with hemophilia and compared with a conventional visual ACT measurement test and with the activated partial thromboplastin time (APTT). ACT values of the 43 dogs used to determine normal values ranged from 66.5 to 97.0 seconds (mean, 79.3 seconds; SD, 7.35 seconds; median, 78.5 seconds). A range of 64-95 seconds (mean +/- 2 SDs) was defined as the normal range for the tested device. Repeatability was poor (r = 0.256). ACT values measured with the automated device did not correlate with ACT values measured with a conventional visual test or with APTT Sensitivity of the test was 90.9%, specificity was 98.0%, and accuracy was 96.7%. Variability in the test results was large and may lead to incorrect results. The automated measurement device was not superior to the conventional visual method in evaluating dogs with hemophilia.

Animals↗

Plasma granulocyte colony-stimulating factor concentrations in neutropenic, parvoviral enteritis-infected puppies.

We evaluated the temporal relationship between neutrophil numbers and plasma granulocyte colony-stimulating factor (G-CSF) concentrations in dogs infected with canine parvovirus, a common infectious cause of neutropenia. G-CSF is produced in response to neutropenia, infection, or inflammation, and results in the production and release of neutrophils from the bone marrow. Adequate numbers of functional neutrophils are necessary for protection from infection, and the timely production of G-CSF is a crucial response to certain diseases. The relationship between peripheral neutrophil numbers and plasma G-CSF concentrations during the course of an infectious disease characterized by neutropenia has not been described previously in dogs. Eight mixed-breed puppies were given an oronasal challenge with canine parvovirus, and peripheral neutrophil numbers as well as plasma G-CSF concentrations were measured daily. G-CSF was not detectable in plasma of any dog before the onset of neutropenia, but G-CSF became detectable just after the onset of neutropenia in the 7 dogs that developed clinical illness. Neutropenia persisted or worsened for at least 2 days after plasma G-CSF became detectable in all 7 dogs. Neutrophil nadir, the highest plasma G-CSF concentrations, and the most severe clinical illness occurred concurrently in most dogs. Although 1 dog died while still neutropenic, plasma G-CSF concentrations declined before resolution of neutropenia in the other 6 dogs, and were again below the limits of detection in 5 of the 6 dogs at the time of resolution.

Animals↗